FDA Allows First Gene Therapy Clinical Trial for Ultra-Rare Pediatric Neurodegenerative Disease

ML4 Foundation-supported program reaches historic first-in-human milestone for children with Mucolipidosis Type IV

ATLANTA, Sept. 2, 2026 /PRNewswire/ -- The Mucolipidosis Type IV (ML4) Foundation announces that the U.S. Food and Drug Administration (FDA) has allowed an Investigational New Drug (IND) application to proceed for the first-ever U.S. clinical trial of an experimental gene therapy for Mucolipidosis Type IV (MLIV), an ultra-rare inherited neurological disease affecting fewer than 100 known children worldwide.

For Randy Gold, President of the ML4 Foundation, and his wife, Caroline, the milestone is deeply personal. Their daughter Eden, now 18, was diagnosed with MLIV as a toddler, inspiring them to help lead the Foundation's effort to develop a treatment.

"When Eden was diagnosed, there was no treatment and only early stage research offering families hope," said Gold. "We became involved because we believed science could offer these children a different future, and we were determined to help make that possible. Now there is an investigational drug developed specifically for MLIV that the FDA has permitted to move into human testing. For our family and every family affected by this disease, that is remarkable."

MLIV is caused by mutations in the MCOLN1 gene, resulting in a deficiency of the protein mucolipin-1 and severe neurological and developmental impairment. Most children with MLIV never learn to walk or talk, typically function at approximately a 15-month developmental level, experience progressive vision loss and have shortened lifespans. There is no approved disease-modifying treatment.

Nearly a Decade of Research

Reaching the clinical trial stage required nearly a decade of scientific, manufacturing and regulatory work coordinated by the ML4 Foundation. The Foundation invested millions of dollars and assembled the team of researchers, clinicians, gene therapy specialists, manufacturers, regulatory experts, donors and affected families needed to translate this treatment from the laboratory to children.

Beginning in 2017, the Foundation made gene therapy a major focus. Research at Massachusetts General Hospital, led by Drs. Susan Slaugenhaupt and Yulia Grishchuk, produced findings by Dr. Grishchuk published in 2021 showing the therapy corrected neurological dysfunction in a mouse model. The Foundation and MGH also established an MLIV Natural History Study documenting disease progression.

In 2023, the Foundation engaged Dr. Miguel Sena-Esteves, Dr. Heather Gray-Edwards and the University of Massachusetts Gene Therapy Center to complete preclinical work and translate the therapy into a clinical program. Work included toxicology studies conducted by Charles River Laboratories; production of clinical-grade drug by Andelyn Biosciences; and extensive stability, sterility, potency, compatibility and dose-related testing, culminating in the IND authorization.

"Developing a gene therapy for an ultra-rare disease presents an incredible challenge," Gold said. "There was no pharmaceutical company waiting to develop this treatment. Families, researchers, donors and supporters had to build the path ourselves. Together we moved this therapy from an idea in a laboratory to an investigational new drug that will now be studied in children."

An Experimental Therapy Targeting the Cause of MLIV

The investigational treatment is designed to address the underlying genetic cause of MLIV. It uses an adeno-associated virus serotype 9 (AAV9) vector to deliver a functional copy of the gene responsible for producing mucolipin-1, with the goal of enabling cells to produce the protein deficient in people with MLIV.

The drug will be administered directly into the brain by a neurosurgeon using a specialized approach designed to reach targeted regions of the central nervous system. Patients will also undergo temporary immune suppression associated with administration of the AAV-based therapy.

Because the treatment has never been administered to a person with MLIV, researchers do not know whether it will provide clinical benefit, the magnitude or timing of any benefit, whether patients will respond similarly, or what adverse effects or unforeseen consequences may occur.

"This is a moment of tremendous hope, but it is also the beginning of the next scientific chapter," Gold said. "The first children who receive this therapy and the families who make that decision will be doing something extraordinary. We do not yet know what the therapy will do. That is precisely why this trial is so important."

Information about the trial, including eligibility and enrollment, will become available as participating institutions complete the remaining institutional and regulatory steps. The Foundation hopes the first children will be treated in 2026.

About the ML4 Foundation

The ML4 Foundation is a family-founded non-profit organization dedicated to improving the lives of children and families affected by Mucolipidosis Type IV and accelerating the development of treatments for the disease.  The Foundation has funded and coordinated basic science, natural history studies, preclinical gene therapy development, manufacturing, toxicology and regulatory activities that have advanced the first experimental MLIV gene therapy to human clinical testing.

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SOURCE The Mucolipidosis Type IV (ML4) Foundation